To test the hypothesis that insulin dependent diabetes millitus in a genetically heterogeneous disease, we propose to study sixty additional families with an insulin dependent diabetic proband for segregation analysis and linkage analysis, using the histocompatibility antigens A, B, C, Dw, and DRw, as genetic markers. Furthermore, over twenty other genetic markers, including blood group antigens, chromosome 6 outside markers, and other markers, will be studied. As a further attempt to resolve the heterogeneity of diabetes, islet cell antibodies, C-peptide, capillary basement membrane thickness, and capillary immunohistochemistry will be measured in many of these families. Further studies will be conducted on five families with maturity onset hyperglycemia in the young.